Control cells are essential for the accuracy and precision of clinical and immunological assays. They are needed to insure the reliability and accuracy of test equipment and methods and to insure reproducibility through time and from laboratory to laboratory. State and federal regulations which govern such assays often require the use of multi-level controls in order to demonstrate that equipment is performing properly over a range of values. In immunological assays, fresh normal cells have been the standard control cells for such equipment testing. In order to avoid the cost and expense of obtaining and maintaining fresh cells, various methods of preserving fresh cells for use as control cells have been evaluated. For example, U.S. Pat. No. 5,059,518 (the '518 patent) describes the use of lyophilized normal cells for use as control cells.
Abnormal blood cell samples have also been used as controls to confirm the presence of a disease or to determine its stage, but their use has been restricted to fresh or refrigerated samples obtained from diseased patients. The supply of such samples is thus inherently restricted, inherently variable and of limited shelf life. Furthermore, since many of such blood samples are also associated with infectious diseases, they are not amenable, for health and social as well as sometimes technical reasons, to large scale production and distribution, and they require special handling procedures.
Some aspects of the problem may be overcome as disclosed in related application Ser. No. 07/944,678 which describes the use of control cells which reflect the abnormal extant state of a blood cell population arising from:
(1) an increase or decrease in the number of cells of a specific type due to the presence of a disease; or
(2) the presence of cells not normally found in normal blood samples, such cells being different in size, shape or other physical characteristics, or having thereon molecules and/or antigenic sites not found on the normal cells.
The control cells of the first type are prepared by depleting a blood sample of specific cells normally present in blood to less than normal levels or by adding such cells to above normal levels and subsequently preserving such samples. The control cells of the second type are prepared by the addition of cells not normally present in a normal blood sample to a normal blood sample and subsequently preserving such sample.
This invention describes a method of preparing, from normal cells or a combination of normal cells and a selected, established cell line, control cells which can be used as an alternative to abnormal cells obtained from patients. To make the control cells of the invention, normal cells obtained from disease free patients or cultured cells are obtained from an established cell line. These cells are subsequently modified, altered or changed to so that they reflect the characteristics of one or more specific cells types which would be present in the blood of a patient having a specific disorder or disease. The normal or cultured cells can also be modified to reflect the characteristics of certain cell types found in tissues as opposed to peripheral blood. For example, normal cells can be modified to reflect the antigenic characteristics of bone marrow cells and derivatives thereof.
The modulation or modification of cells to produce appropriate control cells is not limited to the expression of any one particular cellular constituent and represents a cascade of events reflected in changes in many constituents. Thus the modulation or modification of cells is performed to produce control cells that are appropriate for the constituent(s) being analyzed--be they antigenic constituents as tested by monoclonal antibody binding, enzymatic assays as determined by substrate modification or nucleic acid changes as demonstrated by DNA or RNA probes. The antigenically defined components are, therefore, the endpoint of a cascade of cellular events and the product of DNA/RNA directed biosynthesis.